Preparation of alpha-haloacetamides



United States Patent 3 244,747 PREPARATION OF a-HALQACETAMIDES Kenneth Wayne Ratts, Overland, Mo., assiguor to Monsanto Company, 8t. Louis, Mo., a corporation of Delaware No Drawing. Filed June 2, 1965, Ser. No. 460,867 8 Claims. (Cl. 260-561) This application is a continuation-in-part of application Serial No. 195,974, filed May 18, 1962, by Kenneth Wayne Ratts, and now abandoned.

This invention relates to a method of preparing ochaloacetamides by the hydrolysis of carbamylhalomethylene trisubstituted phosphorane. The preparation of these phosphoranes is described and claimed in a copending application, Serial No. 195,986, filed May 18, 1962 by Angelo John Speziale and the present inventor.

The novel reaction may be defined generically by the equation:

wherein R R and R are selected from the group consisting of cyclohexyl, phenyl and aliphatic hydrocarbon radicals of up to six carbon atoms, including alkyl, alkenyl and alkynyl; wherein R and R are selected from the group consisting of hydrogen atoms, cyclohexyl, phenyl, aliphatic radiacls of up to six carbon atoms, including alkyl, alkenyl and alkynyl radicals, and radicals such that R, and R together are an alkylene radical of 4 to 7 carbon atoms; and wherein X is selcted from the group consisting of chlorine, bromine and iodine.

The novel hydrolysis reaction induces the decomposition of the carbamylhalomethylene trisubstituted phosphorane to a tertiary phosphine oxide and an a-haloacetamide. The hydrolysis may be conducted in the presence of a basic hydrolysis catalyst such as alumina, magnesia, alkali metal hydroxides, for example sodium hydroxide and potassium hydroxide, and alkaline salts of weak acids, for example sodium carbonate and calcium.

In copending application Serial No. 195,986, filed May 18, 1962, there is described and claimed phosphoranes prepared by reacting N,N-substituted carbamylchloromethylene tertiary phosphonium halides with alkaline reagents at 0 to C. The resulting phosphoranes can be further hydrolyzed in accordance with this novel procedure by heating them at temperatures between about C. and the reflux temperature (about 100 to 110 C.). When the reaction involves the use of an alkali metal hydroxide the heat of dilution of the caustic and/or the heat of reaction may be suflicicnt to increase the tempera ture to the required level. The less reactive alkaline reagents, such as magnesia and sodium carbonate require heating from an external source. The use of reflux temperature is a convenient means of supplying the energy necessary for the desired reaction.

Further details are set forth in the following specific examples.

Example 1 N,N diethylcarbamylchloromethylene triphenylphosphorane was suspended in aqueous sodium hydroxide solution. The heat of reaction and the heat of dilution of the caustic increased the temperature to over 50 C. N,N-diethyl ix-chloroacetamide was recovered from the reaction mixture by vacuum distillation.

Example 2 The procedure of Example 1 was repeated except that N,N dia1lylcarbamylbromomethylene trimethylphosphorane was hydrolyzed with sodium carbonate at reflux tem perature of the aqueous suspension. N,N-diallyl a-bromoacetamide is recovered.

Example 3 By the procedure of Example 1, N,N-dipropyl-carbamyl chloromethylene triethylphosphorane was hydrolyzed. N,N-dipropyl m-chloroacetamide was recovered from the reaction mixture.

Example 4 N,N-di-n-butylcarbamyl chloromethylene tricyclohexylphosphorane was hydrolyzed by aqueous sodium hydroxide at to C. N,N-di-n-butyl a-chloroacetamide was thereby produced.

Example 5 The hydrolysis of N,N-propargylcarbamyl chloromethylene trimethylphosphorane at refiuxtemperature in a suspension of magnesia produced N,N-propargyl OL- chloroacetamide.

Example 6 The hydrolysis of N-cyclohexylcarbamyl chloromethylene triethylphosphorane with sodium hydroxide by the procedure of Example 5 produced N-cyclohexyl a-chloroacetamide.

Example 7 By the selction of the proper N,N-substituted carbamylhalomethylene trisubstituted phosphorane the following acetamides are produced by the procedure of Example 1:

N,N-dihexyl a-chloroacetamide N,N-isoamyl a-bromoacetamide N,N-cyclohexyl a-chloroacetamide N-chloroacetyl hexamethylenimine N-chloroacetyl hexamethylenimine N-chloroacetylpiperidine N-phenyl a-chloroacetamide N,N-diallyl a-chloroacetamide Although the invention is described with respect to specific examples, it is not intended that the details thereof are to be construed as limitations on the scope of the invention except to the extent incorporated in the following claims,

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. The method of preparing an a-haloacetamide of the structure wherein R and R are selected from the group consisting of hydrogen, cyclohexyl, phenyl, alkyl having up to six carbon atoms, alkenyl having up to six carbon atoms, and alkynyl having up to six carbon atoms; and wherein X is of the group consisting of chlorine, bromine and iodine; which comprises heating in an aqueous alkaline medium at a temperature between 40 C. and the reflux temperature of the reaction mixture a compound of the structure wherein R R and R are selected from the class consisting of cyclohexyl, phenyl, alkyl having up to six carbon atoms, alkenyl having up to six carbon atoms and alkynyl having up to 6 carbon atoms.

2. The method of preparing a compound of the structure R4 ClCHr( J-N 3 wherein R and R are alkyl radicals having up to six carbon atoms which comprises heating at a temperature above about 40 C. a compound of the structure C1 0 R4 I ll P=GCN\ in the presence of water and sodium hydroxide.

3. The method of preparing a compound of the structure R4 C1CHz( 3N R5 wherein R and R are alkyl radicals having up to six carbon atoms which comprises heating at a temperature above about 40 C. a compound of the structure I ll 4 9)s-P=CCN in the presence of water and magnesia.

4. The method of preparing N,N-diethyl a-chloroacetamide which comprises heating at the reflux temperature N,N-diethylcarbamyl chlorornethylene triphenylphosphorane in an aqueous system in the presence of sodium carbonate.

5. The method of preparing N,N-dipropyl a-Cl'llOl'O- acetamide, which comprises heating at the reflux temperature N,N-dipropy1carbamyl chloromethylene triethylphosphorane in an aqueous system in the presence of an alkali metal hydroxide.

6. The method of preparing N,N-diallyl a-chloroacetamide which comprises heating at the reflux temperature N,N-diallylcarbamyl chloromethylene trimethylphosphorane in an aqueous system in the presence of calcium carbarnate.

7. The method of preparing N,N-dimethyl a-chloroacetamide which comprises heating at the reflux temperature N,N-dimethylcarbamyl iodomethylene triphenylphosphorane in an aqueous system in the presence of potassium hydroxide.

8. The method of preparing NJI-di-n-butyl a-chloroacetamide which comprises heating at the reflux temperature triphenyl N,N-di-n-butyl-carbamyl chloromethylene tricyclohexylphosphorane in an aqueous system in the presence of sodium hydroxide.

N 0 references cited.

WALTER A. MODANCE, Primary Examiner. 

1. THE METHOD OF PREPARING AN A-HALOACETAMIDE OF THE STRUCTURE 